Hydrochloric Acid → 8-Benzyl-8-azabicyclo(3.2.1)octan-3-one

Temperature

0 °C

To cooled 192 ml of 0.025M HCl at 0° C. was added 60 g (454 mmol) of 2,5-dimethoxytetrahydrofuran and the mixture was stirred at 0° C. for 17 hrs. Then sequentially 78 g (543.6 mmol) of benzyl amine, 66 g (452.0 mmol) of 3-oxopentanedioic acid, and 20.4 g (248.4 mmol) of sodium acetate in 360 ml of water was added all at 0° C. The mixture was allowed to warm to room temperature and was stirred at room temperature for 1 hr. The mixture was clear, golden yellow in color. The mixture was heated to 50° C. for 2 hrs. The mixture turned cloudy. The mixture was then cooled to ambient temperature and adjusted to pH˜12 using 50% NaOH in water. The mixture was extracted with ethyl acetate (×3), dried over sodium sulfate and removed solvent to yield a brown oil. The mixture was further purified by distillation, desired product collected ˜120° C. 25 g crude product was recovered as a yellow oil to be carried on to next step.

1. temperatureto warm to room temperature
2. stirringwas stirred at room temperature for 1 hr
3. temperatureThe mixture was heated to 50° C. for 2 hrs
4. temperatureThe mixture was then cooled to ambient temperature
5. extractionThe mixture was extracted with ethyl acetate (×3)
6. dry with materialdried over sodium sulfate
7. customremoved solvent
8. customto yield a brown oil
9. distillationThe mixture was further purified by distillation, desired product
10. customcollected ˜120° C
11. custom25 g crude product was recovered as a yellow oil

ORD record

ord-9b17fdfd5ba5447a8e529358d79324ae

Source dataset

uspto-grants-2010_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07645771B2